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FLASH GENE

Symbol

MEF2A

contributors: mct/ - updated : 22-06-2017

HGNC name	myocyte enhancer factor 2A
HGNC id	6993

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001130926 10 - 5481 NP_001124398 53.3 497 - 2008 18222924 NM_001130927 10 - 5301 NP_001124399 46.4 437 - 2008 18222924 NM_001130928 8 - 5100 NP_001124400 45.4 429 - 2008 18222924 NM_001171894 12 - 5771 NP_001165365 53.7 497 - 2008 18222924

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic monocyte Homo sapiens Lymphoid/Immune macrophage Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

embryo, neonatal

Text	cardiac myocyte

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a MADS(yeast Mcm1, plant homeotic Agamous and Deficiens human Serum response factor) domain at the N terminus mediating dimerization and DNA binding
	immediatly followed by a MEF2 specific domain and forming with it a DNA binding and dimerization domains
	a C terminus required for transcription activation and nuclear localization

HOMOLOGY

intraspecies

paralog to MEF2B

Homologene

FAMILY

MEF2 family

CATEGORY

transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus

basic FUNCTION	associating with HDAC4, HDAC in regulation of skeletal myogenesis
	may be playing an important role in controlling vascular morphogenesis and muscle differentiation and development
	mediating calcium-dependent transcription of the interleukin-2 gene in T lymphocytes
	implicated in neuronal activity-dependent cell survival, and may be regulate excitatory synapse number and postsynaptic differentiation of dendrites
	implicated in the regulation of adult bone mass
	playing a role as an intermediary in coordinating respiratory chain subunit expression in heart and muscle through a NRF1 --> MEF2A --> COX(H) transcriptional cascade
	with MITF function cooperatively with NFATC1 to transactivate the ATP6V0D2 promoter during RANKL-induced osteoclastogenesis
	important component in GNA13-mediated angiogenesis
	possible dual roles of MEF2A and MEF2D in macrophages, as activators or as repressors of gene transcription
	additional role in maintenance of mitochondrial health, a role that may also be shared by other mitochondrial protein synthesis factors
	role in cardiomyocyte survival through regulation of costamere integrity
	indispensable for costamere/focal adhesion integrity and survival of cardiac muscle cells
	nodal point in the reception and interpretation of mechanical signals to promote cytoarchitectural remodeling in cardiomyocytes
	MIR155-mediated repression of MEF2A plays a role in the regulation of muscle gene expression
	key role of MEF2C isoform in the brain, suggesting that MEF2A and MEF2D have only subtle roles in regulating hippocampal synaptic function (
	contrary to skeletal muscle development, MEF2A is required for adult myogenesis in response to injury
	essential role for MEF2A in skeletal muscle regeneration
	distinct roles for MEF2A, PCDH10 and FMR1 in regulated degradation of DLG4 and synapse elimination, suggesting a common deficit in activity-dependent synapse elimination among different genetic causes of autism

CELLULAR PROCESS

nucleotide, transcription

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

	BMP2 and MEF2A are key components of a pathway that controls the cardiac ventricular contractility
	MEF2A-XIRP2 pathway that functions downstream of AGT signaling to modulate its pathological effects in the heart

a component	PIAS2-MEF2A sumoylation signaling link as a key mechanism that orchestrates postsynaptic dendritic claw morphogenesis in the cerebellar cortex and may have novel functions for SUMO E3 ligases in brain development and plasticity
	MEF2A/MEF2D dimers strongly interact with HDAC1, and to a lesser extent with HDAC7 in macrophages, whereas low levels of MEF2A/MEF2D–HDAC1 complexes are found in undifferentiated cells or in monocytes

INTERACTION

DNA	binding to myocyte-specific enhancer

RNA

small molecule

protein	interacting with TWIST to inhibit myogenesis
	interacting with members of the MyoD family of transcriptional activator and with GATA-binding protein, and histone deacetylase
	SLC2A4 and SLC2A4RG (to activate SLC2A4 transcription)
	interacting with NFATC2
	binding SUV39H1 and CABIN1 (targeting its promoter in a calcium-dependent manner)
	interacting with XIRP2
	MEF2C is direct transcriptional target of SOX10 and MEF2A via a evolutionarily conserved enhancer
	XIRP2 and CMYA5 are MEF2A-dependent genes that encode costamere-localized proteins
	MIR155 is an important regulator of MEF2A expression, having a function in muscle gene expression and myogenic differentiation
	repression of MEF2A activity by PRKACA-dependent proteolysis of HDAC4
	molecular interplay of NR3C1 and MEF2A in the control of genes important for neuronal plasticity
	MEF2A directly regulates the MEG3-DIO3 cluster from the MEG3 proximal promoter region
	MEF2A and FMR1 cooperatively regulate the expression of PCDH10
	PCDH10 is required for MEF2A-induced synapse elimination and functions to deliver ubiquitinated DLG4, a critical synaptic scaffolding molecule to the proteasome
	essential and redundant roles of MEF2A, MEF2C, and MEF2D in satellite cell differentiation
	transcription factor MEF2A and PLAGL1 mediate MIF-induced SLC2A4 expression through CD74-dependent AMPK activation in cardiomyocytes
	AKAP6 promotes MYOG expression through myocyte enhancer factor 2A (MEF2A)
	MEF2A and JUN confer antagonistic regulation of HSPB7 gene expression in skeletal muscle, with implications for autophagy and muscle atrophy )

cell & other

REGULATION

activated by

can be activated by BMP2 signaling in neonatal cardiomyocytes

repressed by	HDAC4 through multiple independent repressive domains
		MIR155, that is one of the primary miRNAs that significantly represses the expression of MEF2A

Other	negatively regulated by MITR in association with HDAC1
	regulated by PIAS1 (nuclear E3 ligase, PIAS1, promotes sumoylation of MEF2A, and protein sumoylation could play a pivotal role in controlling MEF2 transcriptional activity)
	sumoylation of MEF2A promotes the differentiation of postsynaptic granule neuron dendritic claws in the cerebellar cortex

ASSOCIATED DISORDERS

corresponding disease(s)

ADCAD1

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   having an impact on histone hyperacetylation in hepatocellular carcinoma constitutional     --low   of endogenous GNA13 and MEF2 proteins in endothelial cells reduced cell proliferation and capillary tube formation

Susceptibility

to myocardial infarction

Variant & Polymorphism SNP	P279L risk factor for myocardial infarction

Candidate gene	for congenital diaphragmatic hernia
Marker
Therapy target	BMP2-MEF2A pathway can offer new opportunities for the treatment of heart failure

ANIMAL & CELL MODELS